Recent findings from a postmortem neuropathologic study in patients with ALS demonstrated TDP-43 inclusions and loss of orexin neurons in the lateral hypothalamus.35 This loss of orexin-producing neurons was related to changes in eating behavior.35 We hypothesize that atrophy of the lateral hypothalamus, which causes a decreased orexin production, explains the relationship between metabolic alterations (weight loss, lower FFM, and decreased mREE) and a reduced volume of the posterior hypothalamus. This evidence concerns the gene HCRT and amyotrophic lateral sclerosis.